Throughout this application various publications are referred to in parenthesis. Citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications are hereby incorporated by reference in their entireties into the subject application to more fully describe the art to which the subject application pertains.
Ricin is a cytotoxic heterodimeric protein isolated from castor beans. Ricin inhibits protein synthesis in cells by cleavage of the N-glycosidic bond of a specific adenosine in a universally conserved GAGA hairpin motif of the 28S subunit of eukaryotic ribosomal RNA (rRNA). The catalytic activity of this heterodimeric protein resides in the ricin toxin A-chain (RTA) and inhibits elongation factor binding to the ribosome, leading to inhibition of protein synthesis and cell death (Endo et al. 1988). The ricin B-chain is a galactose specific lectin that binds to cell surface receptors, thus serving to direct the A-chain for internalization by receptor-mediated endocytosis.
Ricin has very high mammalian toxicity, in the μg/kg range. As such, it has been used in political assassination and has been developed to be used as a terrorist weapon (Hesselberth et al. 2000, Yan et al. 1997). Ricin is categorized as a class B bioterrorist agent. RTA has also been covalently bound to antibodies to be utilized in the design of “magic bullet” immunotoxins, with considerable anticancer activity (Baluna et al. 1999, Engert et al. 1998, O'Toole et al. 1998).
Detection of RTA is important given its potential lethality (Eiklid et al. 1980, Remnick 1992). Current probes for ricin employ ELISA (Shyu et al. 2002), array based immunoassays (Rubina et al. 2005), atomic force microscopy (Maliuchenko et al. 2004), mass spectrometry (Fredriksson et al. 2005) and molecular beacon aptamers (Kirby et al. 2004).